Concentration-time curve of 96% 2,4-D in rat serum.

<p>Mean serum concentration-time profile of 96% 2,4-D after oral administration of 300 mg/kg bw (A) and 60 mg/kg bw (B) to rats (n = 16). Values at 168 h were below the limit of quantification. (OBS means observed value; PRED means predicted value).</p

Mean serum concentration (mg/L) of 2,4-D with time, after oral administration of 300 mg/kg and 60 mg/kg to female and male rats.

<p>Mean serum concentration (mg/L) of 2,4-D with time, after oral administration of 300 mg/kg and 60 mg/kg to female and male rats.</p

Inter- and intra-day precision for determination of 2,4-D in rat serum.

<p>Inter- and intra-day precision for determination of 2,4-D in rat serum.</p

Early-Life Exposure to Bisphenol A Induces Liver Injury in Rats Involvement of Mitochondria-Mediated Apoptosis

<div><p>Exposure to bisphenol A (BPA), a monomer widely used to manufacture polycarbonate plastics, has been reported to be associated with abnormalities of liver function and hepatic damage. However, the molecular mechanism under the pathogenesis of hepatic injury is unclear. In this study, the effect of perinatal exposure to BPA at the reference dose of 50 µg/kg/day on the apoptotic index in the liver of rat offspring was investigated. Increased levels of ALT and enhanced cell apoptosis were observed in the liver of rat offspring at 15 and 21 weeks, and significantly increased activity of caspase-3 and caspase-9 and elevated levels of cytochrome c were also confirmed. In addition, significant change in the expression levels of Bcl-2 and Bax were found in BPA-treated offspring at 21 weeks. For <i>in vitro</i> experiments, liver mitochondria were isolated from neonatal rats and were treated with BPA. BPA treatment led to a significant increase in mitochondrial permeability transition. Moreover, the supernatant from BPA-treated mitochondria significantly increased apoptotic changes in nuclei isolated from liver tissue. In conclusion, the study demonstrates that BPA induces mitochondria-mediated apoptosis in hepatic cells, which may contribute to long-term hepatotoxicity induced by early-life exposure to BPA.</p></div

Effect of BPA on mitochondrial permeability transition (PT) and morphologic features of isolated liver mitochondria.

<p>(A) Changes of PT in the isolated mitochondria with time. Mitochondria isolated from neonatal rat liver were treated with BPA (0 and 1.47 ng/mL) or BPA-glucuronide (2.60 ng/mL). The decrease in optical density measured at 520 nm with time was normalized to 100. Data are shown of three independent experiments. Ultrastructural features of mitochondria treated with the control (B), BPA-glucuronide (C) and BPA (D). Representative images of transmission electron microscopy were shown (magnification, 10,000×).</p

Activity of caspase-3 and caspase-9 in liver tissue after perinatal exposure to BPA.

<p>Activity of caspase-3 (A) and caspase-9 (B) in the liver of 3-week, 15-week and 21-week rat offspring were measured. Values are means ± S.E.M. (n = 6 rats per group; only 1 offspring was selected per litter). *<i>P</i><0.05 compared with controls.</p

Perinatal exposure to BPA increases hepatocyte apoptosis of rat offspring.

<p>(A) Representative images of the TUNEL assay on liver tissue of the control and BPA-treated offspring at 3, 15 and 21 weeks. The TUNEL positive cells increased in the liver of BPA-treated offspring at 21 weeks (magnification, 400×). (B) Percentages of apoptotic cells in the livers from the control group and BPA-treated offspring. Percentages of apoptotic cells were quantified by counting TUNEL-positive cells in 1000 cells in a selected microscopic field per liver section. Data are means ± S.E.M. (n = 6 rats per group; only 1 offspring was selected per litter). *<i>P</i><0.05 compared with controls. (C) Representative images of Hoechst 33258-stained sections of liver tissue from rats of respective group (magnification, 400×).</p

Perinatal exposure to BPA alters the levels of Cyt c, Bcl-2 and Bax.

<p>(A) Western blot analysis of the Cyt c release from mitochondria into the cytosol in rat livers at 3 and 21 weeks. Western blotting analysis of Bax (B) and Bcl-2 (C) in rat offspring liver at 3, 15 and 21 weeks. The protein expression levels were estimated by densitometry with Gapdh as an internal control. Data are expressed as means ± S.E.M. for three independent experiments (n = 6 rats per group; only 1 offspring was selected per litter).). *<i>P</i><0.05 compared with controls.</p

Additional file 1: of Maternal urinary manganese and risk of low birth weight: a case–control study

Distribution of maternal urianry manganese and restricted spline curves association between urinary manganese concentration and risk of low birth weigh in the stratified analysis. (DOCX 104 kb